Voriconazole Accordpharma

Leaflet accompanying the packaging: information for the user

Voriconazole Accordpharma, 200 mg, powder for solution for infusion

Voriconazole

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Voriconazole Accordpharma and what is it used for
• 2. Important information before taking Voriconazole Accordpharma
• 3. How to take Voriconazole Accordpharma
• 4. Possible side effects
• 5. How to store Voriconazole Accordpharma
• 6. Contents of the packaging and other information

1. What is Voriconazole Accordpharma and what is it used for

Voriconazole Accordpharma is an antifungal medicine and contains the active substance — voriconazole. It works by killing fungi that cause infections or by stopping them from growing. It is used to treat patients (adults and children over 2 years of age) with:

• invasive aspergillosis (a type of fungal infection caused by fungi of the genus Aspergillus)
• candidemia (another type of fungal infection caused by fungi of the genus Candida) in patients without neutropenia (in whom there is no decreased number of white blood cells)
• severe invasive Candidainfections that are resistant to fluconazole (another antifungal medicine)
• severe fungal infections caused by fungi of the genus Scedosporiumor Fusarium(two different types of fungi).

Voriconazole Accordpharma is indicated for use in patients with progressive fungal infections that can be life-threatening. It is also used to prevent fungal infections in patients at high risk after bone marrow transplantation. This medicine should only be used under the supervision of a doctor.

2. Important information before taking Voriconazole Accordpharma

When not to take Voriconazole Accordpharma:

It is very important to inform your doctor or pharmacist about all the medicines you are taking or have recently taken, even those that are available without a prescription, or herbal medicines. Do not take Voriconazole Accordpharma at the same time as any of the following medicines:

• terfenadine (used to treat allergies)
• astemizole (used to treat allergies)
• cisapride (used to treat stomach disorders)
• pimozide (used to treat mental illnesses)
• quinidine (used to treat heart rhythm disorders)
• ivabradine (used to treat symptoms of chronic heart failure)
• rifampicin (used to treat tuberculosis)
• efavirenz (used to treat HIV infection) at a dose of 400 mg or higher, taken once a day
• carbamazepine (used to treat epilepsy)
• phenobarbital (used to treat severe insomnia and epilepsy)
• ergot alkaloids (e.g., ergotamine, dihydroergotamine; used to treat migraines)
• sirolimus (used in patients after organ transplantation)
• ritonavir (used to treat HIV infection) at a dose of 400 mg or higher, taken twice a day
• St. John's Wort (herbal medicine)
• naloxegol [used to treat constipation caused by painkillers from the opioid group (e.g., morphine, oxycodone, fentanyl, tramadol, codeine)]
• tolvaptan [used to treat hyponatremia (low sodium levels in the blood) or to slow the progression of kidney disease in patients with polycystic kidney disease]
• luraxadone (used to treat depression)
• venetoclax [used to treat patients with chronic lymphocytic leukemia (CLL)].

Warnings and precautions

Before starting to take Voriconazole Accordpharma, discuss with your doctor, pharmacist, or nurse if:

• the patient has had an allergic reaction to other azole medicines in the past
• the patient has or has had liver disease; the doctor may prescribe a lower dose of Voriconazole Accordpharma; the doctor should also monitor the patient's liver function while taking Voriconazole Accordpharma, ordering appropriate blood tests
• the patient has been diagnosed with cardiomyopathy, irregular heartbeat, slow heart rate, or an abnormality in the electrocardiogram (ECG) known as "prolonged QTc interval".

During treatment, avoid exposure to sunlight. It is essential to protect areas of skin exposed to sunlight and use sunscreens with a high sun protection factor (SPF), as increased skin sensitivity to UV radiation may occur. This may be further increased by other medicines that make the skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children. During treatment with Voriconazole Accordpharma:

• you should immediately inform your doctor if you experience any of the following symptoms:
• sunburn
• severe skin rash or blisters on the skin
• bone pain.

If the above skin disorders occur, your doctor may refer you to a dermatologist, who, after consultation, may decide on the need for regular visits. There is a small risk of developing skin cancer during long-term use of Voriconazole Accordpharma. If you experience symptoms of adrenal insufficiency; in which case the adrenal glands do not produce enough of certain steroid hormones, such as cortisol; which include: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, you should inform your doctor. If you experience symptoms of "Cushing's syndrome", in which the body produces too much of the hormone cortisol, which can lead to symptoms such as: weight gain, appearance of a fatty hump between the shoulder blades, rounding of the face, darkening of the skin on the abdomen, thighs, chest, and arms, thinning of the skin, increased tendency to bruise, increased blood sugar levels, excessive hair growth, excessive sweating, you should inform your doctor. Your doctor should monitor your liver and kidney function with appropriate blood tests.

Children and adolescents

Voriconazole Accordpharma should not be given to children under 2 years of age.

Voriconazole Accordpharma and other medicines

Tell your doctor or pharmacist about all the medicines you are taking or plan to take, including those that are available without a prescription. Some medicines taken at the same time as Voriconazole Accordpharma may change its effect, as well as Voriconazole Accordpharma may affect the action of other medicines. You should inform your doctor if you are taking any of the following medicines, as it is recommended to avoid taking them at the same time as Voriconazole Accordpharma:

• ritonavir (used to treat HIV infection) at a dose of 100 mg, taken twice a day.
• glasdegib (used to treat cancer) - if it is necessary to take both medicines, the doctor will order frequent monitoring of heart rhythm.

You should inform your doctor if you are taking any of the following medicines, as it is recommended to avoid taking them at the same time as Voriconazole Accordpharma. It may also be necessary to modify the dose of voriconazole:

• rifabutin (used to treat tuberculosis); if the patient is already being treated with rifabutin, it will be necessary to monitor blood morphology and observe for side effects related to rifabutin use
• phenytoin (used to treat epilepsy); if the patient is already being treated with phenytoin, it will be necessary to monitor phenytoin levels in the blood during treatment with Voriconazole Accordpharma, and it may also be necessary to modify the dose.

If you are taking any of the following medicines, you should inform your doctor, as it may be necessary to modify or monitor the dosage to ensure that these medicines and/or Voriconazole Accordpharma continue to have the desired effect:

• warfarin and other anticoagulant medicines (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting)
• cyclosporine (used in patients after organ transplantation)
• tacrolimus (used in patients after organ transplantation)
• sulfonylurea derivatives (e.g., tolbutamide, glipizide, and gliburide; used to treat diabetes)
• statins (e.g., atorvastatin, simvastatin; used to lower cholesterol levels)
• benzodiazepines (e.g., midazolam, triazolam; used to treat severe insomnia and stress)
• omeprazole (used to treat stomach ulcers)
• oral contraceptives (if Voriconazole Accordpharma is taken at the same time as oral contraceptives, side effects such as nausea or menstrual disorders may occur)
• vincristine and vinblastine (used to treat cancer)
• tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used to treat cancer)
• tretinoin (used to treat leukemia)
• indinavir and other HIV protease inhibitors (used to treat HIV infection)
• non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine; used to treat HIV infection) (some doses of efavirenz should NOT be taken with Voriconazole Accordpharma)
• methadone (used to treat heroin addiction)
• alfentanil, fentanyl, and other short-acting opioids, such as sufentanil (painkillers used during surgical procedures)
• oxycodone and other long-acting opioids, such as hydrocodone (used to treat moderate or severe pain)
• non-steroidal anti-inflammatory medicines (e.g., ibuprofen, diclofenac; used to treat pain and inflammation)
• fluconazole (used to treat fungal infections)
• everolimus (used to treat advanced kidney cancer and in patients after organ transplantation)
• letermovir [used to prevent cytomegalovirus (CMV) disease after bone marrow transplantation]
• ivacaftor: used to treat cystic fibrosis
• flucloxacillin (an antibiotic used to treat bacterial infections)

Pregnancy and breastfeeding

Do not take Voriconazole Accordpharma during pregnancy, unless your doctor decides otherwise. Women of childbearing age must use effective contraception. If you become pregnant while taking Voriconazole Accordpharma, you should immediately contact your doctor. If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before taking this medicine.

Driving and using machines

Voriconazole Accordpharma may cause blurred vision and discomforting sensitivity to light. Do not drive or operate machinery in such cases. If these disorders occur, contact your doctor.

Voriconazole Accordpharma contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial, which means it is essentially 'sodium-free'.

Voriconazole Accordpharma contains cyclodextrins

This medicine contains 2060.0 mg of cyclodextrin in each vial, which corresponds to 103 mg/ml when dissolved in 20 ml.

3. How to take Voriconazole Accordpharma

Take this medicine always as directed by your doctor. In case of doubt, consult your doctor. The doctor will determine the dose based on the patient's weight and type of infection. The doctor may change the recommended dose depending on the patient's health condition. The recommended dose for adults (including elderly patients) is presented below.

Depending on the response to treatment, the doctor may decide to reduce the dose to 3 mg/kg body weight twice a day. If the patient has mild or moderate liver cirrhosis, the doctor may decide to reduce the dose of Voriconazole Accordpharma.

Use in children and adolescents

The recommended dose for children and adolescents is presented below.

Depending on the patient's response to treatment, the doctor may increase or decrease the daily dose. Voriconazole Accordpharma, powder for solution for infusion, will be dissolved before administration, and the resulting solution will be diluted to the appropriate concentration by hospital staff (see information at the end of the leaflet). The medicine will be administered by intravenous infusion (into a vein) at a maximum rate of 3 mg/kg body weight per hour over 1 to 3 hours. If the patient or child is taking Voriconazole Accordpharma to prevent fungal infections, in the event of side effects related to treatment, the doctor may discontinue Voriconazole Accordpharma.

Missing a dose of Voriconazole Accordpharma

Since the medicine will be administered under close medical supervision, missing a dose is unlikely. However, if a dose is missed, you should always inform your doctor or nurse.

Stopping treatment with Voriconazole Accordpharma

Take Voriconazole Accordpharma for as long as your doctor tells you to. However, treatment with Voriconazole Accordpharma powder for solution for infusion should not exceed 6 months. In patients with weakened immunity or severe infections, long-term treatment may be necessary to prevent the disease from recurring. If clinical improvement occurs, the route of administration of the medicine may be changed from intravenous to oral. If your doctor decides to stop treatment with Voriconazole Accordpharma, you should not experience any effects from stopping it. If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Voriconazole Accordpharma can cause side effects, although not everybody gets them. Most side effects are mild and temporary. However, some of them may be severe and may require medical attention.

Severe side effects — stop taking Voriconazole Accordpharma and contact your doctor immediately

• rash
• jaundice, changes in liver function test results
• pancreatitis.

Other side effects

Very common: may affect more than 1 in 10 people:

• visual impairment (change in vision, including blurred vision, changes in color vision, intolerance to light, color blindness, eye disorders, seeing a rainbow around lights, night blindness, oscillopsia, seeing flashes, visual aura, decreased visual acuity, bright vision, narrowing of the visual field, spots before the eyes)
• fever
• rash
• nausea, vomiting, diarrhea
• headache
• swelling of limbs
• abdominal pain
• breathing difficulties
• increased liver enzyme activity.

Common: may affect up to 1 in 10 people:

• sinusitis, gingivitis, chills, weakness
• low number of certain blood cells, including a significant decrease in the number of red blood cells (sometimes due to immune causes) and/or white blood cells (sometimes accompanied by fever) and/or platelets involved in blood clotting
• low blood sugar levels, low potassium levels, low sodium levels
• anxiety, depression, confusion, agitation, insomnia, hallucinations
• seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations on the skin, increased muscle tension, drowsiness, dizziness
• eye bleeding
• heart rhythm disorders, including very rapid or very slow heart rate, fainting
• low blood pressure, vein inflammation (which may be associated with blood clot formation)
• breathing difficulties with rapid onset, chest pain, facial swelling (of the lips, face, and around the eyes), fluid accumulation in the lungs
• constipation, indigestion, lip inflammation
• jaundice, liver inflammation, liver damage
• rash that can lead to severe blistering and peeling of the skin, characterized by a flat, red area on the skin covered with small merging bumps, redness of the skin
• itching
• hair loss
• back pain
• kidney failure, proteinuria, kidney damage
• sunburn or severe skin reaction after exposure to light or sun
• skin cancer

Uncommon: may affect up to 1 in 100 people:

• flu-like symptoms, gastrointestinal inflammation, antibiotic-associated diarrhea, lymph node inflammation
• inflammation of the thin tissue lining the abdominal cavity and covering the abdominal organs
• enlarged lymph nodes (sometimes painful), bone marrow failure, increased eosinophil count
• adrenal gland disorders, hypothyroidism
• brain disorders, Parkinson's disease-like symptoms, nerve damage causing numbness, pain, tingling, or burning sensations in the hands or feet
• balance or coordination disorders
• brain swelling
• double vision, severe eye disorders, including eye pain and inflammation, abnormal eye movements, optic nerve damage causing vision disturbances, optic disc swelling
• decreased sensitivity to touch
• taste disorders
• hearing loss, ringing in the ears, dizziness
• inflammation of certain internal organs - pancreas and duodenum, tongue inflammation
• liver enlargement, liver failure, gallbladder disease, gallstones
• joint inflammation, vein inflammation under the skin (which may be associated with blood clot formation)
• kidney inflammation, proteinuria, kidney damage
• very rapid or skipped heartbeats, sometimes with abnormal electrical impulses
• abnormal electrocardiogram (ECG) reading
• increased cholesterol levels, increased urea levels in the blood
• allergic skin reactions (sometimes severe), including life-threatening blistering rash and peeling of the skin and mucous membranes, especially in the mouth, skin inflammation, hives, redness and irritation of the skin, purple or red discoloration of the skin, which may be caused by a low platelet count, rash
• reaction at the infusion site
• allergic reaction or excessive immune response.
• inflammation of the tissue surrounding the bone

Rare: may affect up to 1 in 1,000 people:

• hyperthyroidism
• worsening of brain function, a severe complication of liver disease
• optic nerve damage, corneal clouding, involuntary eye movements
• light sensitivity reaction with blistering
• a disease in which the immune system attacks part of the peripheral nervous system
• heart rhythm disorders or conduction disorders (sometimes life-threatening)
• life-threatening allergic reaction
• blood clotting disorders
• allergic skin reactions (sometimes severe), including rapidly progressing swelling of the skin, subcutaneous tissue, mucous membranes, and tissues under the mucous membranes, itching or painful thickened, red skin with silver scales, skin and mucous membrane irritation, life-threatening disease causing large areas of the outer layer of the skin to peel off from the lower layers of the skin
• skin covered with scales, sometimes with thickened, pointed protrusions or "horns".

Frequency not known (frequency cannot be estimated from the available data):

• pigmentation spots on the skin.

Other important side effects, the frequency of which is not known, but which should be reported to your doctor immediately:

• red, scaly patches or skin lesions in a ring shape, which may be a sign of an autoimmune disease called cutaneous lupus erythematosus.

During intravenous administration of voriconazole, the following infusion-related reactions have occurred uncommonly (including flushing, fever, sweating, rapid heart rate, and shortness of breath). If these symptoms occur, your doctor may decide to discontinue the infusion. Due to the known effect of Voriconazole Accordpharma on the liver and kidneys, your doctor should monitor your liver and kidney function with appropriate blood tests. You should also inform your doctor if you experience abdominal pain or changes in stool consistency. In patients treated long-term with Voriconazole Accordpharma, cases of skin cancer have been reported. Sunburn or severe skin reactions due to exposure to light or sun have occurred more frequently in children. If skin disorders occur, your doctor may refer you to a dermatologist, who, after consultation, may decide on the need for regular check-ups. In children, increased liver enzyme activity has also been observed more frequently. If any of these side effects persist or worsen, inform your doctor.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Voriconazole Accordpharma

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and vial after the "EXP" label. The expiry date refers to the last day of the month stated. The batch number on the packaging is stated after the "Lot" abbreviation. Do not store above 30°C. Store in the original packaging to protect from light. The reconstituted concentrate should be used immediately, but if necessary, it can be stored for up to 24 hours at 2-8°C (in a refrigerator) or at room temperature (15-25°C). Before administration, the Voriconazole Accordpharma concentrate should be diluted with the recommended infusion solution (see information at the end of the leaflet). After dilution, the solution may be stored for up to 48 hours at 2-8°C (in a refrigerator) or up to 24 hours at 15-25°C (room temperature). From a microbiological point of view, the prepared solution should be used immediately. Otherwise, the storage time and conditions before use are the responsibility of the user. The storage time of the solution should not exceed 24 hours at 2-8°C (in a refrigerator), provided that the reconstitution (dissolution/dilution) was performed under controlled and validated aseptic conditions. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Voriconazole Accordpharma contains

• The active substance of the medicine is voriconazole.
• The other ingredients are: hydroxypropylbetadex, arginine hydrochloride, sodium hydroxide (to adjust pH), concentrated hydrochloric acid (to adjust pH) (see section 2. Voriconazole Accordpharma contains sodium and cyclodextrins).

Each vial contains 200 mg of voriconazole, and after reconstitution as recommended by the hospital pharmacist or nurse, the concentration of voriconazole is 10 mg/ml (see: information at the end of the leaflet).

What Voriconazole Accordpharma looks like and contents of the pack

Voriconazole Accordpharma is a white or almost white powder for solution for infusion, available in 30 ml glass vials for single use.

Marketing authorization holder and manufacturer

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o. ul. Taśmowa 7, 02-677 Warsaw Tel: + 48 22 577 28 00

Manufacturer

Actavis Italy S.p.A. Via Pasteur 10 20014 Nerviano (MI) Italy S.C. Sindan-Pharma S.R.L. 11th Ion Mihalache Blvd. 011171 Bucharest 1 Romania Accord Healthcare Polska Sp. z o.o. ul. Lutomierska 50 95-200 Pabianice

Date of last revision of the leaflet: February 2025

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Information intended for healthcare professionals only:

Information on reconstitution (preparation of concentrate) and dilution:

• Voriconazole Accordpharma, powder for solution for infusion, should be reconstituted in 19 ml of water for injection or 19 ml of 9 mg/ml (0.9%) sodium chloride injection to obtain 20 ml of a clear concentrate containing 10 mg/ml of voriconazole.
• The vial of Voriconazole Accordpharma should be discarded if, during the introduction of the solvent, it is not drawn into the vial by the existing vacuum.
• To ensure accurate measurement of the volume (19 ml) of water for injection or 9 mg/ml (0.9%) sodium chloride injection, it is recommended to use standard 20 ml (non-automatic) syringes.
• In order to obtain an infusion solution containing 0.5 mg/ml to 5 mg/ml of voriconazole, the required volume of the reconstituted concentrate should be added to the recommended compatible infusion solution (see below).
• The medicinal product is for single use only, and any unused solution should be discarded. Only clear solutions without particles should be used.
• For intravenous use only.
• Information on storage is included in section 5 "How to store Voriconazole Accordpharma".

Required volumes of Voriconazole Accordpharma concentrate 10 mg/ml

Voriconazole Accordpharma is a non-sterile, sterile lyophilisate for single use only. Therefore, from a microbiological point of view, the reconstituted concentrate should be used immediately. If the concentrate is not used immediately, the storage time and conditions before use are the responsibility of the user. The storage time of the concentrate should not exceed 24 hours at 2-8°C (in a refrigerator), provided that the reconstitution was performed under controlled and validated aseptic conditions.

Compatible infusion solutions:

The concentrate can be diluted in: 9 mg/ml (0.9%) sodium chloride injection 5% (50 mg/ml) glucose solution and Ringer's lactate solution for intravenous infusion 5% (50 mg/ml) glucose solution and 0.45% (4.5 mg/ml) sodium chloride injection for intravenous infusion 5% (50 mg/ml) glucose solution for intravenous infusion 5% (50 mg/ml) glucose solution and 20 mEq potassium chloride injection for intravenous infusion 5% (50 mg/ml) glucose solution and 0.9% (9 mg/ml) sodium chloride injection for intravenous infusion Compatibility of Voriconazole Accordpharma with other solutions than those listed above (or listed in the "Incompatibilities" section below) is not known.

Incompatibilities:

Voriconazole Accordpharma must not be infused at the same time as other medicines in the same intravenous line or cannula. This also applies to parenteral nutrition. Voriconazole Accordpharma must not be infused at the same time as any blood product. Intravenous infusion of parenteral nutrition can be administered at the same time as Voriconazole Accordpharma, but not through the same intravenous access or cannula. 4.2% (42 mg/ml) sodium bicarbonate injection for intravenous infusion must not be used to dilute Voriconazole Accordpharma. After reconstitution with water for injection, Voriconazole Accordpharma must not be diluted with 0.45% (4.5 mg/ml) sodium chloride injection or with a complex sodium lactate solution for intravenous infusion due to low osmolality.